Membrane immunoglobulin (mIg) acts as the surface recptor used by B lymphocytes for recognition of antigens. Cross-linkage of mIg leads to activation of the inositol phopholipid metabolic pathway, elevation of cytosolic Ca2+ concentration, and protein kinase C- mediated protein phosphorylation. These events can, in part, be mimicked by the use of ionomycin and phorbol myristate acetate (PMA), pharmacologic agents that elevate cytosolic Ca2+ and that activate protein kinase C. We have recently undertaken a study of the protein substrates phosphorylated in response to PMA and to agents that cross-link mIg. Two of these appear to be of special interest. One, lamin B is a nuclear filament protein that is the major nuclear species phosphorylated in cells treated with PMA. Lamin B is phosphorylated in vivo in a pattern very similar to that observed for in vitro phosphorylation of partially purified lamin B by PKC, suggesting that PKC or PKC-like kinase gains access to the nucleus and phosphorylates substrates in that site. This provides ameans for the rapid transmission of surface signal to the nucleus. The second major substrate pp66-70 is one of the major myristylated proteins of the cell. pp65-70 is expressed in substantial amounts in B cells and B lymphomas such as WEHI-231 but mature T cells fail to express pp65-70. Immature thymocytes display large amounts of pp65-70 while more mature thymocytes express only small amounts of pp65-70 indicating that this PKC- substrate is developmentally regulated. The means through which receptor cross-linkage leads to activation of cellular biochemical signals is still unrresolved. Efforts to understand the molecular requirements for signal generation through the creation of chimeric genes that express the external domains of class I or class II MHC molecules and the transmembrane and cytoplasmic domains of Ig (mu, delta, gamma 2b) and the examination of their capacity to transmit signals are in progress.